Prescription opioid misuse and addiction among active duty service members (ADSM) with chronic pain present significant public health threats to the U.S. Military. Many ADSM suffer from persistent pain conditions incurred in the line of service that require appropriate medical treatment with opioids. Yet, a substantial subset of ADSM with chronic pain is at risk for developing opioid addiction. Opioid addiction among persons with chronic pain involves cognitive, affective, and behavioral dysregulation that often results in serious functional impairment and health risks. Addiction to prescription opioids may emerge from prolonged engagement in opioid misusing behaviors, such as dose escalation, use of illicit opioids, or use of opioids to self-medicate negative emotions. Although opioid delivery systems with lower addiction liability have been developed, extant treatments have low rates of successful outcomes in the absence of maintenance pharmacotherapy. Moreover, persons seeking treatment for chronic pain respond especially poorly to existing addictions treatments. Conventional pharmacotherapies may have limited efficacy without long-term maintenance because they fail to target and durably alter dysregulated cognitive-affective habit circuits which govern appetitive responses elicited by pain, stress, and drug cues. As such, prevention interventions are urgently needed to effectively address key cognitive-affective mediators of the risk chain from chronic pain to opioid misuse and addiction among ADSM. We propose to test a novel selective prevention intervention, Mindfulness-Oriented Recovery Enhancement (MORE), which integrates mindfulness training, cognitive reappraisal, and enhancement of natural reward processing to augment psychological health and break the cycle of pain, craving, and negative affect leading to the development of opioid addiction. The overarching aim of this proposal is to determine whether MORE reduces opioid misuse and prevents the development of opioid addiction among ADSM with chronic pain who are in the reintegration stage of the Military Lifecycle and exhibiting opioid misuse behaviors. A sample of 120 opioid misusing ADSM with chronic pain will be recruited from Fort Carson, CO, and randomly assigned to 8 group sessions of MORE or a conventional support group (SG). Assessments will be conducted at pre- and post-treatment, as well for 6 monthly follow-ups. We hypothesize that MORE will result in significantly greater reductions in opioid misuse (primary outcome) than the SG, as well as significantly greater decreases in opioid craving and pain (secondary outcomes). We hypothesize that clinical outcomes will be mediated by changes in attentional bias (AB), emotion regulation, autonomic cue-reactivity, and positive psychological processes. Furthermore, we hypothesize that AB and cue- elicited heart rate variability following treatment will predict the occurrence and timing of relapse to opioid misuse. R34 funding for this early stage randomized controlled trial will allow for a rigorous test of an innovative prevention intervention for ADSM grounded in models from cognitive, affective, and neurobiological science. This R34 proposal builds on the PI's decade-long clinical and research work in this area, including his prior NIDA-funded R03.